GLP-1 weight-loss medicines have changed the conversation around obesity. Semaglutide, sold as Ozempic and Wegovy, and the related drug tirzepatide, sold as Mounjaro and Zepbound, produce weight loss that diet alone rarely matches. But there is a catch that gets less attention than it should, and it is where diet, including keto, becomes relevant. This is a summary of what the research shows, not a how-to, because these are prescription medicines and how you use them is a matter for you and your doctor.
The problem: not all the weight lost is fat
When people lose weight quickly, some of what they lose is muscle as well as fat, and the weight-loss drugs are no exception. Recent research has put numbers on it: a 2025 pooling of trials found that, on average, roughly a quarter of the weight lost on GLP-1 medication came from lean mass rather than fat, and some studies have reported higher figures still. Losing muscle matters. It weakens you, it lowers the rate at which your body burns energy at rest, and it can make weight regain easier later. So a sensible goal while losing weight, on a drug or otherwise, is to lose as much fat and as little muscle as possible.
Where diet comes in
Muscle is built and defended largely by two things: eating enough protein and using the muscles, particularly through resistance exercise. Those are the established levers, and they apply to anyone losing weight. The newer question is whether the type of diet alongside the medication makes a difference to how much muscle is spared, and that is what a 2025 study set out to test.
The 2025 study
Schiavo and colleagues, writing in the journal Nutrients, ran a 12-week pilot study in 60 people with obesity, all taking tirzepatide. Half followed a low-energy ketogenic plan, very low in carbohydrate and relatively high in protein, and half followed a standard low-calorie diet with the same calories. The interesting part is what happened to muscle when the weight loss itself was similar between the groups.
What it found
Both groups lost a similar amount of weight, around 10 per cent, but the makeup of that loss differed sharply. The ketogenic group lost almost no fat-free mass, around half a per cent, while the standard low-calorie group lost over four per cent. Muscle strength held steady in the keto group and dropped noticeably in the other. Resting metabolic rate, the energy you burn just existing, fell much less on keto. And the keto group lost slightly more actual fat. In short, for the same weight on the scales, the ketogenic approach appeared to protect muscle, strength and metabolism considerably better.
What the study does not tell us
This is a genuinely interesting result, and it needs its limits stated plainly. It was a small pilot of 60 people, it was not randomised, it ran for only 12 weeks, and it included no structured exercise programme, which is itself one of the strongest tools for protecting muscle. It also used tirzepatide specifically, not semaglutide, so while the drugs are closely related the finding is strictly about the one that was tested. One promising pilot is a reason for larger trials, not a settled conclusion.
The honest takeaway
Put together, the research suggests two things. First, anyone losing weight on a GLP-1 medicine should care about protecting muscle, because a meaningful slice of the loss otherwise comes from there. Second, the well-established ways to protect it are eating enough protein and doing resistance exercise, and a higher-protein, lower-carbohydrate pattern like keto is an emerging and plausible addition that one early study found helpful. A simple, sustainable approach to the exercise side pairs naturally with that.
What this is not is a recommendation to combine a prescription drug with a strict diet on your own initiative. These medicines affect appetite, blood sugar and more, and stacking a very-low-calorie or very-low-carb diet on top changes the equation in ways that need medical oversight. The research is worth knowing so you can have a better-informed conversation; the decisions belong with your prescriber.
The bottom line
GLP-1 weight-loss drugs work, but a large share of the weight lost can be muscle. The proven defences are protein and resistance training, and a 2025 pilot study found that a ketogenic approach preserved muscle, strength and metabolic rate better than a standard low-calorie diet at the same weight loss. It is early evidence, from one small study using tirzepatide, and a reason for interest rather than a protocol to follow alone.
This is general information, not medical advice. Semaglutide and tirzepatide are prescription-only medicines. Do not start, stop, change, or combine any medication or restrictive diet without the guidance of the doctor who prescribes for you.
Source: Schiavo L, et al. Preliminary Evidence Suggests That a 12-Week Treatment with Tirzepatide Plus Low-Energy Ketogenic Therapy Is More Effective than Its Combination with a Low-Calorie Diet in Preserving Fat-Free Mass, Muscle Strength, and Resting Metabolic Rate in Patients with Obesity. Nutrients. 2025. Read it here.